Liu Guang, Qi Xiaoyong, Li Xingtao, Sun Fangyi
Department of Cardiovascular Medicine, Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
Department of Cardiovascular Medicine, Hebei General Hospital, Shijiazhuang, Hebei 050000, P.R. China.
Exp Ther Med. 2021 May;21(5):473. doi: 10.3892/etm.2021.9904. Epub 2021 Mar 11.
Trastuzumab (TZM) significantly improves the outcomes of patients with breast cancer; however, it is associated with severe cardiotoxicity. Ginsenoside Rg2 was reported to exert protective effects against myocardial injury and apoptosis in human cardiomyocytes (HCMs). However, whether ginsenoside Rg2 protects HCMs against TZM-induced toxicity remains unclear. The present study investigated the proliferation of HCMs using a Cell Counting Kit-8 assay and Ki67 immunofluorescence staining. Apoptotic cells were detected by Annexin V/propidium iodide staining and flow cytometry. Furthermore, monodansylcadaverine staining was performed to detect cell autophagy. In addition, western blotting was used to detect the expression levels of phosphorylated (p)-Akt, p-mTOR, beclin 1, microtubule associated protein 1 light chain 3α (LC3) and autophagy protein 5 (ATG5) in HCMs. Pretreatment with ginsenoside Rg2 significantly protected HCMs against TZM-induced cytotoxicity by inhibiting apoptosis. Furthermore, pretreatment with ginsenoside Rg2 induced autophagy in HCMs by upregulating the expression levels of p-Akt, p-mTOR, beclin 1, LC3 and ATG5. The results obtained in the present study suggested that ginsenoside Rg2 could protect HCMs against TZM-induced cardiotoxicity by activating autophagy. Therefore, ginsenoside Rg2 may serve as a potential therapeutic agent to prevent TZM-related cardiotoxicity in patients with breast cancer.
曲妥珠单抗（TZM）显著改善了乳腺癌患者的预后；然而，它与严重的心脏毒性有关。据报道，人参皂苷Rg2对人心肌细胞（HCMs）的心肌损伤和凋亡具有保护作用。然而，人参皂苷Rg2是否能保护HCMs免受TZM诱导的毒性尚不清楚。本研究使用细胞计数试剂盒-8检测法和Ki67免疫荧光染色来研究HCMs的增殖情况。通过膜联蛋白V/碘化丙啶染色和流式细胞术检测凋亡细胞。此外，进行单丹磺酰尸胺染色以检测细胞自噬。另外，采用蛋白质免疫印迹法检测HCMs中磷酸化（p）-Akt、p-mTOR、贝林1、微管相关蛋白1轻链3α（LC3）和自噬蛋白5（ATG5）的表达水平。人参皂苷Rg2预处理通过抑制凋亡显著保护HCMs免受TZM诱导的细胞毒性。此外，人参皂苷Rg2预处理通过上调p-Akt、p-mTOR、贝林1、LC3和ATG5的表达水平诱导HCMs自噬。本研究结果表明，人参皂苷Rg2可通过激活自噬保护HCMs免受TZM诱导的心脏毒性。因此，人参皂苷Rg2可能作为一种潜在的治疗药物，用于预防乳腺癌患者中与TZM相关的心脏毒性。
